C. RENAL REPLACEMENT Flashcards
what is dialysis
diffusion of molecules in solution across a semi-permeable membrane along electrochemical conc gradient (high to low)
what % of CKD patients progress to end-stage renal failure and hence need RRT
2%
what is dialysis used for
- correct fluid and electrolyte imbalances
- remove nitrogenous waste products
what are the 4 types of dialysis
- haemodialysis (HD)
- haemodiafiltration (HDF)
- peritoneal dialysis (PD)
- continuous haemofiltration methods (CHF) - expensive
why is dialysis NOT a cure for kidney failure
- doesn’t correct endocrine functions of kidney: can’t manage vitamin D levels, calcium absorption, EPO stimulation etc
- eGFR will still be <15ml/min/1.73m2
- can still progress and may need a transplant
what is haemofiltration
- based mainly on convection, pumped through a system incorporating a semi-permeable membrane
- the pressure on the blood side pushes plasma across the filter (ultrafiltration)
- molecules that are small enough <50,000 daltons are pulled across with water in convection
what is haemodiafiltration
- combines convention and diffusion
- convection is the process during which solutes and solvent move according to the pressure gradient
indications for dialysis
- fluid overload not responding to diuretics
- uremic convulsions (uric acid in blood (uraemia), into brain)
- persistent dyspnoea (due to build up of N waste), vomiting, restlessness
- signs of pericarditis, pericardial effusion
- profound electrolyte abnormalities
- eGFR <15ml/min/1.73m (most common reason)
process for a patient with renal failure
- pre-dialysis clinic
- peritoneal dialysis (less invasive)
- haemodialysis
- transplant
- pre-dialysis clinic for monitoring
pre-dialysis clinic
- aka ‘low clearance clinic’
- patient assessed for suitable type of RRT with their lifestyle etc
- aims to slow time until RRT is required
what are the 2 types of peritoneal dialysis
- CAPD (continuous ambulatory peritoneal dialysis)
- Automated peritoneal dialysis
principles of CAPD
- uses patients body as a filter
- the peritoneal membrane is semi-permeable
- the dialysate bag contains neutral fluid to create conc grad
- dialysate inserted into peritoneal space
- repeated cycle of instilling dialysate solution into cavity through catheter
- managed by patient at home
- doesn’t interfere with life as much
- dialysate with waste drained into drainage bag
- risk of skin infections/cellulitis due to tubing from external to internal
- 1.5-3L fluid each time for 4x daily (bigger patient needs for fluid)
- the drainage bag is below the catheter site so it drains via gravity (bag strapped to leg, catheter under clothes)
*synthetic membranes bind larger drugs combined with modified cellulose
principles of automated peritoneal dialysis
- solution changed by machine at night
- exchanges 8-12L during 8-10 hours (asleep)
principles of hameodialysis
- remove blood for cleaning
- a sonication device: low frequency sound waves which disturb blood, loosens it up and removes waste products
- arterial pressure monitor
- LMW heparin pump to prevent clotting: as blood is passed out, through tubes and then back in, if clots in tubes could lead to stroke
- through dialyser (artificial kidney)
- venous pressure monitor to check blood isn’t too high/low a pressure
- clean blood into patient
- Involves blood being pumped through a system that incorporates a dialyser
- In the dialyser blood is separated from a crystalloid solution (dialysate) by a semi-
permeable membrane - Solutes move across the membrane via a concentration gradient from one compartment to another by obeying ‘Fick’s law of diffusion’
- blood and solution is flowing in opposite directions to maintain conc grad
when is haemodialysis required
- someones kidneys have failed to a point that if we do not intervene they may die
questions to ask patient about dialysis
- where is your dialysis done
- what days do you get dialysis done – affects when we give drugs as otherwise will be filtered out
where, when, how often is HD done
- 3x a week
- specialist dialysis clinics (not every hospital)
- each sessions lasts 2-4 hours
- patients read, write, sleep, walk, watch TV
factors that affect removal of substances for HD
- SA, type & permeability of dialyser
- Blood flow rate
- Dialysate flow rate
- Duration of dialysis
- Drug: MW, protein binding
factors that affect removal of substances for PD
- Conc grad between dialysate and plasma
- Peritoneum permeability (as get older, it decreases)
- Volume and frequency of changes
- Drug: Vd, protein binding, renal excretion
how are small molecules removed
diffusion
how are larger molecules removed
convection
properties of drugs most likely to be dialysed
- low MW (larger will diffuse more slowly)
- (HD < 500 Da, HDF < 20,000 Da as using convection aswell)
- low protein binding
- small Vd (<1L/kg) as lots of drug is concentrated in the circulatory system and not passed into external tissues
- water soluble (as hydrophilic)
- renally cleared (>50%)
ideal drug for a renal patient
- non-renal excretion
- no SEs
- active drug
- no renally excreted metabolites
*odd to get all these for one drug!
complications with HD
- Hypotension
- Muscle cramps
- Clot formation (hence use heparin)
(main 3^) - Sepsis
- Hepatitis
- Disequilibrium syndrome
complications with PD
- Protein loss
- Exit site infection
- Peritonitis (change to HD?)
- Abdominal pain
- Hernia
- Lower back pain
- Pneumonia
role of pharmacist in RRT
- Check what type of dialysis the patient has
- Find out what days the patient has dialysis on, and for how long each
dialysis session lasts - If they have it at a dialysis unit, which dialysis unit are they under and who is the consultant in charge
- Is the dialysis unit aware that their patient has been admitted (Most hospitals have dialysis but it may be a satellite of another hospital)
can 1 kidney achieve normal kidney function
yes
treatment of choice for ESRD
- renal transplant - improves survival and offers better QoL
- lowers morbidity and mortality rates
the 2 sources of organs
- deceased donors (non-heart-beating)
- living donors (heart-beating) (related or non-related)
what medicines may be required for renal transplant patients
- Immunosuppression, unless an identical twin (usually tacrolimus (Adoport) +/- mycophenolate +/-
Prednisolone) - Prophylaxis medicines
- Pain relief and laxatives
- Pharmacist may be required to review pre-surgery medicines
- May require stress ulcer prophylaxis
- may need to stop anti-coagulants before surgery
donor and recipient matching
- blood group matching
- tissue type matching
- cross matching
*applies to living and deceased kidney donation
blood group matching
- Type O most common (type O can donate to type O, A, B, AB)
- then A (type A can donate to type A, AB)
- then B (type B can donate to type B, AB)
- then AB (type AB can donate to type AB)
tissue type matching
- Known as HLA testing (Human Leukocyte Antigen)
- Out of >100 antigens, 6 are important in transplantation
- Inherit 3 from each parent
- Except in identical siblings, chance of a 6 antigen match is 1 in 100,000 (normally 2/3 match with donor)
- In some cases transplants with no matching antigens are not rejected
- No way to predict who will experience rejection
- 6 antigen matches allow for decreased immunosuppressive use
cross matching
- Very important part of the work up
- Repeated just before surgery
- Blood from donor and recipient is mixed
- Looking for recipient cells to attack donors
- Means recipient has antibodies against the donor
- Cannot go ahead if this occurs
how does rejection occur
- patient’s white blood cells reduce or stop the function of the transplanted kidney
- same way as it fights bacteria / an infection
symptoms of rejection
- Fever
- Decreased urine output
- Fluid retention
- Increase in weight
- Tenderness over the kidney
- Elevated blood pressure
*most rejection episodes can be reversed with drug treatment but may need to take kidney out
hyper acute rejection
- occurs minutes or hours after the transplant
- this type is very rare, untreatable and the kidney is removed immediately
acute rejection (most common)
- can happen at any time after a transplant
- serum creatinine rises (as using old kidneys)
- can usually be treated with a higher dose or different type of immunosuppressive medicine until the creatinine returns to baseline
chronic rejection
- may develop after months or years
- there is no known treatment as already on immunosuppressives so they mustn’t be working
3 classifications of immunosuppressive regimens
- induction
- maintenance
- antirejection
induction regimens
- usually higher doses
- provide intense early postoperative immune suppression
- use monoclonal or polyclonal ABs
maintenance regimens
- used throughout the patient’s life to prevent both
acute and chronic rejection (bigger role for specialist pharmacist prescribers)
types of maintenance immunosuppressive drugs
- Antiproliferative Immunosuppressants
- Azathioprine
- Mycophenolate Mofetil / Mycophenolic Acid (Myfortic) MOST COMMON - Calcineurin Inhibitors
- Ciclosporin (BRAND specific if using oral form) NEXT MOST COMMON
- Tacrolimus (BRAND specific if using oral form!)
this is due to different release kinetics - mTOR Inhibitors
- Sirolimus (BRAND specific if using oral form!) - Corticosteroids
- Prednisolone: usually life-long and may be doubled in acute situations
why are transplant patients usually very compliant
- patients realise rarity of a transplant and must look after it
- do not want to jeopardise – unlikely to get a second transplant
other support drugs for renal transplant
- Antibiotic prophylaxis
- Co-trimoxazole (for PCP) – normally taken for 12 months after transplant - Antifungal prophylaxis
- Nystatin (gels etc) – normally taken for 3 months after transplant - Antiviral prophylaxis
- Valganciclovir – normally taken for 100 days after transplant - Tuberculosis prophylaxis
- Isoniazid and Pyridoxine – usually for first 12 months after transplant if indicated (ie at risk)